P2 Calcium Induced Intramitochondrial cAMP Signalling Enhances Aldosterone Secretion

DOI

10.2991/artres.k.191224.037How to use a DOI?

Abstract

Elevation of plasma [K⁺] and [angiotensin II] (Ang II), two major physiological stimuli of adrenal zona glomerulosa cells, increase aldosterone production by triggering cytosolic Ca²⁺ signalling. Cytosolic Ca²⁺ signals are accompanied by mitochondrial Ca²⁺ elevations which further strengthen this steroidogenic response. It has recently been recognized that such mitochondrial Ca²⁺ signals activate the mitochondrial soluble adenylyl cyclase (sAC) thus evoking intramitochondrial (matrix) cAMP elevations during Ca²⁺ signalling. We hypothesised that this Ca²⁺ induced mitochondrial cAMP production, too, contributes to the hypersecretion of aldosterone. Using human adrenocortical H295R cells we found that silencing of sAC decreased mitochondrial cAMP production and, at the same time, decelerated Ca²⁺ accumulation by the organelle. On the other hand, inhibition of the mitochondrial phosphodiesterase (PDE2A) intensified matrix cAMP production and accelerated mitochondrial Ca²⁺ uptake. More importantly, both pharmacological inhibition and knock-down of sAC mitigate AngII-induced aldosterone production. Finally, overexpression of wild-type sAC within the mitochondrial matrix increased mitochondrial cAMP formation, accelerated mitochondrial Ca²⁺ uptake and, most prominently, potentiated aldosterone production as compared to the enzymatically inactive mutant enzyme. Altogether, Ca²⁺-induced mitochondrial cAMP signalling supports aldosterone production by favouring additional Ca²⁺ influx into the organelle. This positive feed-back loop may expedite the hormonal response when immediate hypersecretion of mineralocorticoids is crucial for cardiovascular compensation (e.g. exsiccation, blood loss).

Copyright

© 2019 Association for Research into Arterial Structure and Physiology. Publishing services by Atlantis Press International B.V.

Open Access

This is an open access article distributed under the CC BY-NC 4.0 license (http://creativecommons.org/licenses/by-nc/4.0/).

TY  - JOUR
AU  - Gergő Szanda
AU  - Éva Wisniewski
AU  - Anikó Rajki
AU  - András Spät
PY  - 2020
DA  - 2020/02/15
TI  - P2 Calcium Induced Intramitochondrial cAMP Signalling Enhances Aldosterone Secretion
JO  - Artery Research
SP  - S44
EP  - S44
VL  - 25
IS  - Supplement 1
SN  - 1876-4401
UR  - https://doi.org/10.2991/artres.k.191224.037
DO  - 10.2991/artres.k.191224.037
ID  - Szanda2020
ER  -